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GSE45382
Mus musculus
4 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
F4/80+ macrophages treated with TGFb2 are potently tolerogenic. Our understanding of the molecular mechanisms mediating the development of these tolerogenic properties is incomplete.
Publication Title
FcγRI is required for TGFβ2-treated macrophage-induced tolerance.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 165 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
To investigate the cellular responses induced by air pollution exposures, we performed genome-wide gene expression microarray analysis using whole blood RNA sampled at three time-points across the work weeks of 63 non-smoking employees in the trucking industry. Our objective was to identify the genes and gene networks differentially activated in response to micro-environmental measures of occupational exposure to three pollutants: PM2.5 (particulate matter 2.5 microns in diameter) and elemental carbon (EC) and organic carbon (OC).
Publication Title
Gene expression network analyses in response to air pollution exposures in the trucking industry.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
The potential safety issues related to the acquisition of common genomic aberrations in hPSC cultures are well-recognized, but these risks have not been evaluated for sporadic mutations. Here, we explore whether a sporadic mutation that spontaneously arose in a hESC culture consisting of a single-copy deletion of chr17p13.1 would confer a survival advantage to the mutant cells. Compared to wild-type cells with two normal copies of the chr17p13.1 region, the mutant cells displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of pluripotent cells after two weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. RNA sequencing analysis showed differential expression of genes in pathways related to proliferation and differentiation. Thus, phenotypic implications of sporadic mutations must be taken into consideration before using the hPSC for clinical applications. Overall design: Triplicate cDNA libraries of two mutant WA09 lines with a single-copy deletion of chr17p13.1, and two wild-type WA09 lines, for a total of 12 libraries were sequenced using Illumina HiSeq 2500. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.
Publication Title
Spontaneous Single-Copy Loss of TP53 in Human Embryonic Stem Cells Markedly Increases Cell Proliferation and Survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 313 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Whole human fetal lung transcriptome profiles from estimated gestational ages 54 to 137 days post conception. Maternal cigarette smoking status is indicated by cotinine levels measured in the corresponding placenta.
Publication Title
Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Peripheral whole blood transcriptome profiles of pregnant women enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
Publication Title
The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
Sample Metadata Fields
Sex, Specimen part, Treatment, Race
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Tacrolimus and Sirolimus are commonly used to maintain immunosuppression in kidney transplantation. However, their effects on immune cells and allograft molecular profiles have not been elucidated.
Publication Title
Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage.
Publication Title
c-Met-dependent multipotent labyrinth trophoblast progenitors establish placental exchange interface.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 157 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Peripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and preeclampsia from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Publication Title
Early pregnancy vitamin D status and risk of preeclampsia.
Sample Metadata Fields
Sex, Race
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level of gene expression using a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many of the up-regulated genes encoded molecules were involved in immune response and inflammation, transcription, signalling, apoptosis, cell cycle, electron transport and cell adhesion. Of particular interest was the up-regulation of proinflammatory cytokines, typical of the classically activated macrophages (M1 phenotype) such as TNF-?, IL-1 and IL-6, and also the up-regulation of anti-inflammatory mediators such as IL-1ra and IL-10 associated with macrophage alternative activation (M2 phenotype). Furthermore, the gene encoding inducible nitric oxide synthase (iNOS), an enzyme typically implicated in classical activation was not induced in infected macrophages. Instead, the gene encoding arginase, a competitor for the iNOS substrate arginine and involved in the alternative activation pathway was up-regulated in S. pyogenes-infected cells. Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes induced an atypical activation program in macrophages with some but not all features of classically or alternatively activation phenotypes. The microarray data also suggested that the bactericidal activity of macrophages against S. pyogenes is mediated by phagocyte oxydase since p47phox was up-regulated in infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was markedly diminished in the absence of functional phagocyte (p47phox-/-) but not in the absence of iNOS (iNOS-/-). Understanding how macrophages respond to S. pyogenes at the molecular level may facilitate the development of new therapeutic paradigms.
Publication Title
Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 384 Downloadable Samples
- NextSeq 500
Description
Immune checkpoint blockade has shown tremendous anti-tumor potential in the clinic. However, these therapies are only effective in a subset of patients, so identification of additional immunomodulatory molecules that enhance the anti-tumor activity of these treatments may expand their clinical utility. In particular, identifying small molecules that complement existing immunotherapies has been relatively unexplored, so we performed a small molecule screen to identify compounds that can enhance co-inhibitory molecule blockade, to improve the anti-tumor adaptive immune response. Our unbiased screen identified inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6), including the FDA-approved palbociclib, as a class of small molecule compounds that exhibited significant immunostimulatory activity in vitro. In accordance with our in vitro finding of enhanced NFAT signaling, single-cell RNA-sequencing confirmed that in vivo exposure to CDK4/6 inhibitors enhanced NFAT signaling in tumor infiltrating T cells. Moreover, our results revealed that CDK4/6 inhibition up-regulated activation molecules and down-regulated suppressive molecules in these cells. CDK4/6 inhibition also increased the number of T cells with activated TCR (T cell receptor) signaling, as well as factors that are important for signal transduction downstream of TCR signaling. In summary, the impact of CDK4/6i on cell cycle progression and T cell proliferation are balanced favorably towards increased T cell recruitment and enhanced effector cell function, mediated in part by activation of the NFAT family of transcription factors. Further, our results demonstrate that CDK4/6i enhances PD-1 blockade through increased T-cell effector function and inhibition of immune suppressive cytokine production. While prolonged CDK4/6i treatment could be immunosuppressive due to adverse effects on lymphocyte proliferation, properly timed/sequenced CDK4/6i may potentiate the clinical impact of anti-PD-1/PD-L1 antibodies. As palbociclib is FDA-approved and multiple other CDK4/6 inhibitors are in clinical trials, we expect that this hypothesis will undergo rapid testing in humans. Overall design: Single-cell comparison of control and CDK4/6 inhibitor treated tumor infiltrating T cells
Publication Title
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples